Pyridine carboxylic acid



Patented Apr. 25, 1944 .rrammn CABBOXYLIC acm Alfred 'r. Hawkinson. and Artlmr a. Elston,

Niagara Falls, N. Y., assignors to E. I. du Pont de Ncmours & Company, Wilmingt corporation of Delaware on, Del., a

No Drawing. Application November 21, 1941, 562181 No. 420,690

11 Claims. (01. zoo-295.5)

This invention relates to a new and improved process for the manufacture of pyridine carboxylic acids, especially quinolinic and nicotinic acids. More particularly, it relates to an improved method for preparing nicotinic acid from salts, particularly the heavy metal salts, of pyridine monocarboxylic and pyridine dicarboxylic acids.

Heavy metal salts of the pyridine monocarboxylic and pyridine dicarboxylic acids may ordinarily be prepared by the oxidation of pyridine derivatives, such as quinoline and related compounds. In .preparing these heavy metal salts quinoline and other related compounds such as the various lutidines, alphaand beta-picolines, nicotine, etc., are ordinarily oxidized by treatment with oxidizing agents. The resulting acids may be isolated by conversion to the form of their salts, generally the copper salts thereof. This invention is particularly concerned with a new and improved process for securing nicotinic acid in a very pure form from the heavy metal salts, particularly the copper salts of the pyridine monocarboxylic and dicarboxylic acids such as copper nicotinate, or copper quinolinate.

The isolation of the free nicotinic acid in the past has been accomplished by treating a water suspension of copper quinolinate or copper nicotinate with hydrogen sulfide or with an alkali metal sulfide such as sodium sulfide. In this process the copper is converted to the insoluble copper sulfide and there remains an aqueous solution of the free acid or of an alkali metal salt of the organic acid. Treating the copper or other heavy metal salt of the pyridine monocarboxylic or dicarboxylic acid in this way requires the introduction of a considerable excess of the sulfide. Moreover, the copper sulfide is secured in a form wherein it is extremely difficult to remove it eifectively by filtration. These disadvantages have been accompanied by a decreased yield, believed to be attributable to coating of the insoluble heavy metal salt such as copper quinolinate or copper 'nicotinate with a iayer of insoluble copper sulfide, this layer preventing further reaction between the organic copper salt and the hydrogen sulfide or inorganic sulfide.

It has been proposed, particularly in the recovery of picolinic acid from copper picolinate, to treat the solution of the organic acid salt with caustic soda. While this method possesses some advantages and can be efiectively used in treating salts such as copper quinolinate or copper nicotinate as well as copper plcolinate, it also possesses many disadvantages. These disadvantages are generally similar to those accompanying the use of the previously referred to sulfide method of recovery.

We have been particularly concerned with the manufacture of nicotinic acid from the heavy metal, especially copper salts, of quinolinic or nicotinic acids by a method wherein the nicotinic acid is produced in the highest possible state of purity. This process involves treatment or the insoluble copper organic salt of the pyridine carboxylic acid in order to convert it to a soluble form. The solution is then treated to convert the salt to the form of the free pyridine car-- boxylic acid. When this acid is a dicarboxylic acid such as quinolinic acid, it is next necessary to treat that acid in order todecarboxylate it and convert it to the form of nicotinic acid. In

carrying out these processes it is necessary that the solution resulting from dissolving the heavy metal salt shall be as pure as possible, so that the final product, nicotinic acid, shall be secured as a colorless, substantially pure compound.

We have now discovered that by utilizing ammonia or ammonium hydroxide in order to bring the heavy metal, particularly copper salt or salts of the pyridine monoor dicarboxylic acids, into solution, certain distinct advantages accrue which result in improving the purity of the product. Moreover, we have found that the free inorganic acid may :bereadily dissolved in acetic acid under such conditions that inorganic impuritiesqiresent are left behind as insoluble residues. When decarboxylation to nicotinic acid is necessary, as for example when that acid is prepared from quinolinic acid,.such decarboxylation is also most effectively carried out in the acetic acid solution.

Accordingly, it is a primary object of our invention to produce nicotinic acid of high purity andfof high yields from the heavy metal salts, particularly copper salts of the pyridine mono-' carboxylic and dicarboxylic acids such as nicotinic and quinolinic acids. Another object of this invention is the development of a process for recovering nicotinic acid under circumstances wherein the formation of objectionable inorganic or organic by-products during the operations is avoided, particularly those inorganic or organic by-products which are soluble in the organic solvent used during the latter stages of the process wherein the acid is separated fromthe inorganic impurities present. This object may be summarized by stating that it is our desire to prepare nicotinic acid under conditions wherein both organic and inorganic impurities.

Still further objects of our invention involve the development of a process wherein the copper is separated from the rganic salt of the pyridine utilization as a catalyst or precipitant in the production of further amounts of nicotinic acid, and the development of a process which will permit the reutilization of the copper in this way constitutes still another object of thisinvention. These objects of our invention, as well as other which will be noted hereinafter, are attained by preparing the nicotinic acid by an improved process, certain preferred embodiments of which are set forth in the ensuing disclosure.

Our process consists of dissolving the heavy metal salt of a pyridine carboxylic acid in ammonia solution, precipitating the heavy metal oxide by addition of a strong inorganic alkali, separating the precipitated copper oxide in the usual manner; then acidifying the solution to set free the pyridine carboxylic acid and evaporating the solution to dryness. As a final step the pyridine carboxylic acid is dissolved in a suitable anhydrous organic acid, from which it may be separated by crystallization or evaporation of the solvent. The final step includes, in the case of pyridine dicarboxylic acids, the operation of heating said acids in contact with the anhydrous organic acid in order to bring about decarboxylation to the monocarboxylic acid.

In describing our improved procedure for the manufacture of pyridine carboxylic acids in high yields and ina high degree of purity, we will generally refer herein to the production of quinolinic and nicotinic acids from copper quinolinate. Copper quinolinate can be regarded as a typical heavy metal salt of a pyridine monocarboxylic or dicarboxylic acid, the treatment of which in accordance with our process constitutes ou-- improved procedure. However, other similar heavy metal salts may be similarly treated, as may the copper or other similar heavy metal salts of the various pyridine acids. Thus, while copper quinolinate is taken as a typical example of the starting product which is to be treated in accordance with our process to produce nicotinic acid as a desired end product, the process is equally applicable when salts of other acids, such as copper nicotinic and cinchomeronic acids, are so treated.

The copper salt, such for example as copper quinolinate, may be produced. in various ways, as by the oxidation of quinoline or lutidine. In carrying out this oxidation various oxidizing agents such as potassium permanganate, nitric acid, hydrogen peroxide, etc., may be utilized for oxidizing the quinoline or its related compounds. In our copending application Serial No. 401,674, filed July 9, 1941, we have disclosed a process wherein quinoline is oxidized with hydrogen peroxide in an aqueous solution containing an organic acid and a heavy metal salt. While it is not necessary that the copper or other heavy metal salt be produced by any specific process, and any of various oxidizing agents may be used, we prefer to employ copper quinolinate produced by the oxidation of quinoline with hydrogen peroxide in the presence of acetic acid and copper acetate, as disclosed in our copending application. The copper quinolinate may be either wet sodium quinolinate.

; the compound is secured in a high state of purity, -one characterized by the substantial absence of or dry as it comes directly from the oxidation process, and the salt is usually in the form of the dihydrate.

The copper quinolinate dihydrate, taking the treatment of that salt as typical of our process, is first suspended in suflicient water to form a thin slurry. The amount of water utilized is not critical, amounts ranging from 2 to 3 parts of water per part of copper salt being generally suflicient. The slurry is subjected to moderate agitation and concentrated ammonium hydroxide is then preferably added in amount sufilcient to cause complete solution of the copper quinolinate. Other ammonia-liberating compounds besides ammonium hydroxide are suitable, among which may be mentioned ammonium salts such as ammonium carbonate. However, we prefer to use concentrated ammonium hydroxide (28% NH; concentration), and have found that one part of this solution per part of copper quinolinate salt is sufficient to bring the salt into solution. While larger amounts than this may be utilized, they are not essential, and the use of smaller amounts of ammonia will of course bring into solution only a part of the copper.

The resulting solution of copper quinolinate in aqueous ammonia is then treated with a solution of sodium hydroxide or other alkali. Generally we prefer to utilize alkali metal hydroxides such as sodium hydroxide or potassium hydroxide, but other alkaline compound such as the carbonates, may be utilized. e amount of alkali added should be sufficient at least to form the disodium salt of quinolinic acid. Preferably we prefer to add an excess of the alkali, and have found that an excess of from to 100% of caustic is sufficient to insure satisfactory precipitation of copper oxide. The preferred amounts are therefore 1 part by weight of sodium hydroxide or other alkali for each 2 parts of copper quinolinate dihydrate. The concentration of the caustic solution added is not critical, but we have found it convenient to add it in the form of a 20 to 50% aqueous solution.

The solution is now warmed or heated until it becomes black in color due to the formation' of copper oxide. Although not unduly critical, we have found it desirable to heat the solution to a temperature of at least 40 to C. in order to hasten formation of the copper oxide. Temperatures in excess of 60 C. may be employed with equal success, as the solution may be boiled without deleteriously affecting the process.

The precipitated copper oxide is next filtered from the solution. Copper oxide precipitated in the manner specified may be filtered from the solution very readily. On the other hand, we have found that when copper oxide is precipitated by adding alkali to a suspension of copper quinolinate, as practiced in processes now known to the art, the resulting precipitate of copper oxide is exceedingly difficult to filter.

We next.prefer to eliminate free ammonia present in th filtrate containing the dissolved While the removal of ammonia at this stage is not absolutely essential, it is advisable since it reduces the quantity of acid required to liberate the quinolinic acid during the next step of the process, as well as the amount of inorganic salts formed on neutralization of the solution. The free ammonia is preferably liberated by boiling the solution for from 10 to 20 minutes. After driving off the excess ammonia in this way, the solution is then neutralized with an inorganic acid to a pH falling within the rang 3 to 5. While any inorganic acid such as sulfuric acid or hydrochloric acid may be employed in the neutralization, ordinarily we prefer to utilize hydrochloric acid. It the solution exhibits any objectionable color at this stage, it mayadvantageously be removed by treating the solution with decolorizing carbon.

The quinolinic acid is now in the form of the free acid and may be secured by evaporation to dryness. Accordingly, we prefer to evaporate the solution at this stage to dryness, thereby securing a dry mixture of the free quinolinic acid, an alkali metal salt of the acid used in the neutralization, and a small amount of ammonium chloride. The-crude product may be dried at a temperature of 110-120 C. to produce a dry solid product.

The crude mixture of quinolinic acid and salt which has been thoroughly dried is then covered with glacial acetic acid in a closed container which is fitted with an air-cooled or water-cooled reflux. The mixture is heated at the boiling point of acetic acid until the evolution of carbon dioxide ceases. In this way one carboxyl group is removed from quinolinic acid, thereby forming the desired product, nicotinic acid. Of course, if the product at this stage is in the form of nicotinic acid, as would result, for example, when copper nicotinate is treated in accordance with our improved process, decarboxylation is not necessary.

The amount of glacial acetic acid utilized is not critical, and we have found that from 2 to 4. parts of the glacial acid for each part of crude product treated is sufllcient. The completeness of'decarboxylation may be determined by taking a small sample of the mixture, diluting it with water, and neutralizing the solution with caustic to a pH within the range 7.0 to 8.0. If decarboxylation is not complete a reddish color will develop if a few drops of ferrous sulfate are added to the neutral solution. Heating the organic acid salt with glacial acetic acid solution should be continued until substantially no color is developed when the ferrous sulfate test is applied.

when decarboxylation is complete the hot glacial acetic acid solution is filtered to remove th insoluble inorganic salt, leaving a solution of nicotinic acid. If there is any objectionable color present at this stage, it may be advantageous to add a small amount of decolorizing carbon to the hot acid solution before filtering. After filtration the nicotinic acid may be recovered by cooling to room temperature or thereabouts, whereupon the nicotinic acid will crystallize. If desired, the nicotinic acid may be recovered by distilling off the glacial acetic acid, the pure nicotinic acid remaining behind as the residue.

The copper oxide precipitated from the ammoniacal solution of the copper salt of the organic acid during an earlier stage of our process may be readily recovered for reutilization in our process. The copper oxide should first be well washed with water to free it from adhering sodium quinolinate solution, the washings being included with the main body of the filtrate. It is thentreated with a suitable acid to recover the copper in the form of a salt thereof. Generally we prefer to utilize acetic acid so as to regenerate the copper acetate catalyst referred to in our copending patent application.

When other heavy metal salts of pyridine monocarboxylic acids such, for example, as copper nicotinate, are treated in accordance with our improved process, the procedure is the same except, of course, that it is necessary in that case to heat the glacial acetic acid solution only until the nicotinic acid is completely dissolved. Since decarboxylation is not carried out under these circumstances, tests for completeness of decarboxylation are not necessary,

While we prefer to utilize glacial acetic acid for decarboxylating quinolinic acid and for separating the resulting nicotinic acid from inorganic residues, other substantially an drous acids such as formic acid and propionic ac d may be utilized. If desired, decarboxylation may be carried out by heating the mixture of quinolinic acid and salt in the dry state, thn separating the resulting nicotinic acid from the inorganic residues with hot glacial acetic acid. Decarboxylation may also be carried out in concentrated hydrochloric solution under pressure, followed by distilling off the hydrochloric acid and separating the nicotinic acid from the residue with glacial acetic acid. However, the method herein described, wherein glacial acetic acid is used, is our preferred method because of its convenienceand ease of operation.

In obtaining the solid organic acid we prefer to evaporate the solution to dryness as described above. However, if desired, the solution may be evaporated to a small volume of liquid, cooled, the organic acid permitted to crystallize, recovered, and then subjected to drying. Similarly, the recovery of nicotinic acid from glacial acetic acid may be carried out by distilling or evaporating the solution to a small volume, whereupon the. nicotinic acid will crystallize out in a very pure form upon further cooling,

As examples of our improved process for preparing nicotinic acid in very pure form from heavy metal salts of the pyridine monocarboxylic and dicarboxylic acids, the following may be given.

Example 1 Fifty parts of copper quinolinate dihydrate was prepared by oxidizing quinoline with hydrogen,

added to the ammoniacal copper quinolinate solution. The solution was heated to a temperature of C. for from ten to fifteen minutes, or until no trace of blue color was visible in the solution. The precipitated copper oxide was then filtered off and the cake thoroughly washed with water. The washings were added to the main body of filtrate, which was then boiled until only a slight odor of ammonia remained. The clear solution was then cooled, neutralized by the addition of concentrated hydrochloric acid to a pH of 2.0 to 4.5, treated with approximately three parts of "Darco decolorizing carbon, and filtered. Upon evaporation to dryness, 68 parts of a mixture of quinolinic acid and sodium chloride, this mixture containing a small amount of ammonium chloride, was obtained.

The quinolinic acid-salt mixture was then covered with 200 parts of glacial acetic acid in a closed vessel equipped with a reflux condenser. It was refluxed for from two to four hours, until the ferrous sulfate test previously described indicated decarboxylation was complete. About two parts of Darco decolorizing carbon was then added and the solution was filtered. The salt residue remaining was washed with two or three small portions of glacial acetic acid and the washings added to the main filtrate.

The glacial acetic acid was then distilled from the filtg'ate. There then remained in the still at the completion of distillation a product which, when dried in a current of warm air until free from the odor of acetic acid, yielded 21 parts of product in the form of pure white crystals.

The resulting product had a melting point of 232 C., a neutralization equivalent of 119, and assayed 100% nicotinic acid by the sublimation method described on page 610 of Official and Tentative Methods of Analysis of the Association of Oflicial Agricultural Chemists, 5th edition It was thus pure nicotinic acid crystals, free from any discoloring matter.

In the foregoing example all parts given are by weight.

Example 2 Copper nicotinate was prepared by the oxidation of beta-picoline with potassium permanganate, followed by precipitation with copper sulfate. Fifty parts of this product was then treated as described in Example 1. However, in treating the mixture of acid and salt with glacial acetic acid, heating was carried out only for a time sufficiently long to insure complete solution of the nicotinic acid.

The product was pure nicotinic acid having a melting point of 232 C., and the yield amounted to 38.5 parts. All parts given are by weight.

It should be understood that various changes may be made in our process as herein described without affecting the improved results attained. Thus, various modifications of conditions as to time, temperature, alkalinity, acidity, etc., and various changes in procedure differing from those herein given as illustrative of the preferred embodiments of our invention may be made without departing from the scope thereof. Accordingly, the scope of our invention is to be determined in accordance with the prior art and appended claims.

We claim:

1. The .method for preparing a pyridine carboxylic acid from a heavy metal salt selected from the group which consists of the ammonia-soluble heavy metal salts of pyridine monocarboxylic and dicarboxylic acids which comprises the steps of; dissolving said heavy metal salt in an aqueous ammoniacal solution; adding a strong inorganic alkali to the resulting solution in order to precipitate heavy metal oxide therefrom, thepyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing the precipitated heavy metal oxide; and adding a mineral acid to said solution in order to convert said metal salt of said pyridine carboxylic acid to the free acid.

2. The method for preparing a pyridine carboxylic acid from a copper salt selected from the group which consists of copper salts of pyridine monocarboxylic acids and copper salts of pyridine dicarboxylic acids which comprises the steps of preparing an aqueous ammoniacal solution of said copper salt; adding a strong inorganic alkali to the resulting solution in order to precipitate copper oxide therefrom, the pyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated copper oxide; and adding a mineral acid thereto in order to convert said metal salt of said pyridine carboxylic acid to the free acid.

3. The method for preparing a pyridine carboxylic acid from a copper salt thereof selected from the group which consists of copper quinolinate and copper nicotinate which comprises the steps of preparing an aqueous ammoniacal solution of said copper salt; adding a strong inorganic alkali thereto in order to precipitate copper oxide therefrom, the pyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated copper oxide; and adding a mineral acid thereto in order to convert said metal salt of said pyridine carboxylic acid to the free acid. a

4. The method for preparing quinolinic acid from an ammonia-soluble heavy metal salt thereof which comprises the steps of; dissolving said heavy metal salt in an aqueous ammoniacal solution by bringing said salt into contact with an ammonia-liberating compound in aqueous solution; adding a strong inorganic alkali to the resulting solution in order to precipitate heavy metal oxide therefrom, the quinolinic acid remaining in said solution in the form of an alkali metal salt thereof; removing said precipitated heavy metal oxide; and adding a mineral acid to said clear solution in order to convert said alkali metal salt of quinolinic acid to the free acid.

5. The method for preparing nicotinic acid from an ammonia-soluble heavy metal salt thereof which comprises the steps of; dissolving said heavy metal salt in an ammoniacal solution by bringing said salt into contact with an ammonialiberating compound in aqueous solution; adding a strong inorganic alkali to the resulting solution in order to precipitate heavy metal oxide therefrom, the nicotinic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated copper oxide; and adding a mineral acidthereto in order to convert said alkali metal salt of nicotinic acid to the free acid.

6. The method of preparing a pyridine carboxylic acid in the dry state from a heavy metal salt selected from the group which consists of theammonia-soluble heavy metal salts of pyridine monocarboxylic acids and Pyridine dicarboxylic acids which comprises the steps of; dissolving said heavy metal salt in an ammoniacal solution by bringing said salt into contact with an ammonia-liberating compound in aqueous solution; adding a strong inorganic alkali thereto in order to precipitate heavy metal oxide therefrom, the pyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated heavy metal oxide; adding a mineral acid to the resulting clear solution in order to convert said alkali metal salt of said pyridine carboxylic acid to the form of the free acid; and then evaporating said solution to dryness in order to recover said pyridine carboxylic acid in the dry state.

'7. The method of preparing a pyridine carboxylic acid in the dry state from a copper salt of a pyridine monocarboxylic or pyridine dicarboxylic acid which comprises the steps of; dissolving said copper salt in an ammoniacal solution tion in order to convert said alkali metal salt of said pyridine carboxylic acid to the free acid; and

evaporating said solution to dryness in order to recover said pyridine carboxylic acid in the dry state.

8. The method for preparing a pyridine carboxylic acid selected from the group which consists of quinolinic acid and nicotinic acid in .the dry state from a copper salt thereof which comprises the steps of dissolving said copper salt in an aqueous ammoniacal solution; adding a strong inorganic alkali to said solution in order to p cipitate copper oxide therefrom, the pyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated copper oxide; boiling said solution in order to drive out a portion of the residual ammonia; adding a mineral acid to said solution in order to convert said alkali metal salt of pyridine carboxylic acid to the free acid; and evaporating said solution to dryness in order to recover said pyridine carboxylic acid in the dry state.

9. The method for preparing quinolinic acid in the dry state from copper quinolinate which comprises the steps of dissolving said copper quinolinate in an ammoniacal solution by bringing it into contact with an ammonia-liberating compound in aqueous solution; adding a strong inorganic alkali to the resulting solution in order to precipitate coppe'r oxide therefrom, the quinclinic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated copper oxide; boiling said resulting clear solution in order to free it from a portion of the residual ammonia; adding a mineral acid to said solution in order to convert said alkali metal salt of quinolinic acid to the free acid; and then evaporating said solution to dryness in order to recover said free acid in the solid state.

10. The method for preparing nicotinic acid in the dry state from copper nicotinate which com prises the steps of dissolving said copper nicotinate in an ammoniacal solution; adding a strong inorganic alkali to the resulting solution in order to precipitate copper oxide therefrom, the pyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated copper oxide; boiling said resulting clear solution in order to drive out a portion of the residual ammonia; adding a mineral acid to said solution in order to convert said alkali metal salt of nicotinic acid to the free acid; and then evaporating said solution to dryness in order to recover said nicotinic acid in the dry state.

11. The method for preparing a pyridine carboxylic acid from a heavy metal salt selected from the group which consists of the ammoniasoluble heavy metal salts of pyridine monocarboxylic acids and pyridine dicarboxylic acids which comprises the steps of; dissolving said heavy metal salt in an ammoniacal solution by bringing said salt into contact with an ammonialiberating compound in aqueous solution; adding a strong inorganic alkali to the resulting solution in order to precipitate the heavy metal oxide, the pyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing said precipitated heavy metal oxide; adding a mineral acid to the resulting clear solution in order to convert said alkali metal salt of said pyridine carboxylic acid to the free acid; and evaporating said solution to dryness in order to secure a dry mixture of free pyridine carboxylic acid and inorganic salt impurities.

12. The method for preparing a pyridine carboxylic acid selected from the group which consists of nicotinic acid and qulnolinic acid from a copper salt thereof which comprises the steps of; dissolving said copper salt in an aqueous ammoniacal solution; adding a strong inorganic alkali to the resulting solution in order to precipitate copper oxide, the pyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated copper oxide;adding a mineral acid to the resulting clear solution in order to convert said alkali metal salt of pyridine carboxylic acid to the free acid; and evaporating said solution to dryness in order to secure a dry mixture of free pyridine carboxylic acid and inorganic salt impurities.

13. The method for preparing a pyridine carboxyhc acid from a heavy metal salt selected froin the group which consists of the ammoniasoluble heavy metal salts of pyridine monocarboxylic acids and pyridine dicarboxylic acids winch comprises the steps of dissolving said heavy metal salt in an aqueous ammoniacal solution; adding a strong inorganic alkali thereto in order to precipitate heavy metal oxide, the pyridine carboxylic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated heav metal oxide; adding a mineral acid to the resulting clear solution in order to convert said alkali metal salt of pyridine carboxylic acid to the free acid; evaporating the resulting solution to dryness in order to secure a dry mixture of free pyridine carboxylic acid and inorganic salt impurities; dissolving said dry mixture in a substantially anhydrous organic acid selected from the group which consists of glacial acetic acid, anhydrou formic acid, and anhydrous propionic acid; removing the undissolved morgamc impurities from the resulting solution; and recovering said substantially pure pyridine carboxylic acid from said solution.

14. The method for preparing a pyridine carboxylic acid selected from the group which consists of quinolinic acid and nicotinic acid from a copper salt thereof which comprise the steps of; dissolving said copper salt in an aqueous ammomacal solution; adding a strong inorganic alkali to the resulting solution in order to precipitate copper oxide; removing said precipitated cop-- per oxide; adding a mineral acid to the resulting clear solution in order to convert said pyridine carboxylic acid to the free acid; evaporating said solution to dryness in order to secure a dry solid mixture of said pyridine carboxylic acid and inorganic salt impurities; dissolving said dry solid mixture in a substantially anhydrous organic solvent selected from the group which consists of glacial acetic acid, anhydrous formic acid, and anhydrous propionic acid; removing undissolved inorganic salt impurities from the resulting solution; and treating said -resulting clear solution in order to recover said pyridine carboxylic acid iii the pure state.

15. The method for preparing nicotinic acid in the substantially pure state from copper quinolinate which comprises the steps of; dissolving said copper quinolinate in an aqueous ammoniacal solution; adding a strong inorganic alkali to the resulting solution in order to precipitate copper oxide therefrom, the quinolinic acid remaining in said solution in the form of an alkali metal salt thereof; removing precipitated copper oxide; adding a mineral acid to the resulting clear solution in order to convert said alkali metal salt of said quinolinic acid to the free acid; evaporating said copper nicotinate in an aqueous ammoniacal solution; adding a strong inorganic alkali to the resulting solution in order to precipitate copper oxide therefrom, the nicotinic acid remaining in said solution in the form or an alkali metal salt thereof; removing precipitated copper oxide; adding a strong mineral acid to the resulting clear solution; evaporating said solution to dryness in order to secure a dry mixture of free nicotinic acid and inorganic salt impurities; dissolving said dry mixture in glacial acetic acid;

freeing the resulting solution from undissolved inorganic salt impurities present therein; and treating said resulting solution in order to secure salt: nicotinic acid in the substantially pure. dry sta e.

17. The method for preparing nicotinic acid in the substantially pure state from an ammoniasoluble heavy metal quinolinate which comprises the steps of; dissolving said heavy metal quinolinate in an aqueous ammoniacal solution; adding a strong inorganic alkali to the resulting solution in order to precipitate heavy metal oxide therefrom; removing precipitated heavy metal oxide from said solution; adding a mineral acid to the resulting clear solution; evaporating said solution to dryness in order to secure a dry mixture of quinolinic acid and inorganic salt impurities; decarboxylating said quinolinic acid in order to prepare nicotinic acid; and recovering said nicotinic acid in the substantially pure state from the resulting mixture.

ALFRED T. HAWKINSON. ARTHUR A. EISTON. 

